DNA damage checkpoint response to aflatoxin B1

ENGİN A. B., Engin A.

ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, vol.65, pp.90-96, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 65
  • Publication Date: 2019
  • Doi Number: 10.1016/j.etap.2018.12.006
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.90-96
  • Keywords: Aflatoxin B1, Aflatoxin B1-8,9-epoxide, Aflatoxin B1-E-N7-dG adduct, Ataxia telangiectasia mutated kinase, DNA damage checkpoints, Hepatocellular carcinoma, BRONCHIAL EPITHELIAL-CELLS, TUMOR-SUPPRESSOR GENE, HEPATOCELLULAR-CARCINOMA, DEATH RECEPTOR, SIGNAL-TRANSDUCTION, CELLULAR-RESPONSES, INDUCED ACTIVATION, TP53 MUTATIONS, CYCLE ARREST, LOPHIRONES B
  • Gazi University Affiliated: Yes


Although most countries regulate the aflatoxin levels in food by legislations, high amounts of aflatoxin B1 (AFB1)-DNA adducts can still be detected in normal and tumorous tissue obtained from cancer patients. AFB1 cannot directly interact with DNA unless it is biotransformed to AFB1-8, 9-epoxide via cytochrome p450 enzymes. This metabolite spontaneously and irreversibly attaches to guanine residues to generate highly mutagenic DNA adducts. AFB1-induced mutation of ATM kinase results in the deterioration of the cell cycle checkpoint activation at the G2/M checkpoint site. Genomic instability and increased cancer risk due to A T mutation is the result of diminished repair of DNA double strand breaks. The major point mutation caused by AFB1 is G-to-T transversion that is related with the high frequency of p53 mutation. Majority of AFB1 associated hepatocellular cancer cases carry TP53 mutant DNA, which is an indicator of AFB1 exposure, as well as hepatocellular cancer risk.